Last year we have accomplished the following:(i) uncovered an essential physiological function of uteroglobin (UG) by targeted disruption of the UG gene in embryonic stem cells. Mice, homozygous (-/-) for UG gene disruption, develops a severe fibronectin(Fn)-deposit glomerulonephritis, an inflammatory disease of the kidneys. The results of this study show that UG is, indeed, an endogenous antiinflammatory agent and raise the possibility that the molecular mechanisms of a human hereditary Fn-deposit glomerulonephritis, may be very similar, if not identical to that of the UG-knockout mice; (ii) in a related study, we have developed a transgenic murine model of eotaxin overexpression in the airway. Since eotaxin is a chemokine which attracts eosinophils and eosinophilia of the airway is a hallmark of asthma, we expect that full characterization of this animal model will allow us to gain insight into the mechanism of pathogenesis of this relatively common inflammatory disease; (iii) demonstrated that uteroglobin regulates cell motility via a high-affinity receptor expressed on several cell types; (iv) discovered that a high-affinity cell surface receptor for group I phospholipase A2 (PLA2) induces cellular invasion of the extracellular matrix and this receptor is expressed at a high level in several tumor cell lines; (v) demonstrated that NF IL-6 is essential for the induction of cyclooxygenase-2 gene expression by group I pancreatic PLA2 in MC-3T3 cells; (vi) cloned and characterized a cDNA and the gene for murine group I pancreatic PLA2 and its differential tissue-specific expression in the mouse; (vii) using an antisense mouse model which expresses osteopontin (OPN) antisense mRNA under the regulation of MMTV-LTR causes severe abnormality in mammary gland ductal differentiation suggesting that OPN may play a critical role in the development of this organ;(viii) cloned and characterized the cDNA and the gene encoding murine protein palmitoyl thioesterase, an enzyme that catalyzes the depalmitoylation of lipid-modified proteins and reported to be mutated in infantile neuronal ceroid lipofuscinosis (INCL), a neurodegenerative disease in children without an effective therapy.